Chemical mixtures: challenge for toxicology and risk assessment.


:It is now well-recognized that human environmental exposures are not to single chemicals. Rather, humans are exposed, either concurrently or sequentially, to multiple chemicals. Challenges that chemical mixtures pose for risk assessment and toxicology are presented. Challenge areas include increasing the peer-reviewed publication of human studies, improving access to peer-reviewed data and examining multiple target organs. Two difficult challenges are development of a common, consistent language and the use of appropriate and innovative experimental designs and analyses. The challenge of elucidation of mechanism(s) offers a rational basis for extrapolation across dose levels, exposure durations and exposure routes as well as to other species and to other similar chemicals. Of particular importance is focusing effort on those areas of investigation where answers have the greatest potential for reducing uncertainty in risk assessments for chemical mixtures and on those chemical mixtures and multiple chemical exposures that have the greatest potential impact on human health. A particularly fruitful area for future investigation is determination of the likelihood of nonadditive interactions in humans exposed to multiple chemicals at environmental exposure levels.






Simmons JE




Has Abstract


1995-12-28 00:00:00














  • Investigations in bitro and in vivo, of the effects of disulfiram (Antabuse) on human lymphocyte chromosomes.

    abstract::Pilinskaya showed that the fungicide ziram induced chrocosome aberrations in the lymphocytes of exposed industrial workers and also in lymphocyte cultures treated in vitro. Ziram is chemically similar to the drug Antabuse (disulfirm) which is used in the treatment of alcoholics. To establish whether disulfirm can also...


    pub_type: 杂志文章


    authors: Lilly LJ

    更新日期:1975-07-01 00:00:00

  • Dose metric considerations in in vitro assays to improve quantitative in vitro-in vivo dose extrapolations.

    abstract::Challenges to improve toxicological risk assessment to meet the demands of the EU chemical's legislation, REACH, and the EU 7th Amendment of the Cosmetics Directive have accelerated the development of non-animal based methods. Unfortunately, uncertainties remain surrounding the power of alternative methods such as in ...


    pub_type: 杂志文章,评审


    authors: Groothuis FA,Heringa MB,Nicol B,Hermens JL,Blaauboer BJ,Kramer NI

    更新日期:2015-06-05 00:00:00

  • Teratogenic effects of various di-n-butyltins with different anions and butyl(3-hydroxybutyl)tin dilaurate in rats.

    abstract::In our previous study, di-n-butyltin diacetate has been shown to cause malformations such as cleft mandible, ankyloglossia, fused ribs, etc. in rat fetuses after oral treatment of maternal rats on day 8 of gestation. In this study, teratogenic effects of five di-n-butyltin compounds with different anions and also buty...


    pub_type: 杂志文章


    authors: Noda T,Morita S,Baba A

    更新日期:1993-12-31 00:00:00

  • Allergenicity evaluation of p-chloro-m-cresol and p-chloro-m-xylenol by non-radioactive murine local lymph-node assay and multiple-dose guinea pig maximization test.

    abstract::p-Chloro-m-cresol (PCMC) and p-chloro-m-xylenol (PCMX) are known to cause allergic contact dermatitis. For risk assessment of skin sensitizers, information on dose-response profiles in the induction and elicitation phases and cross-reactivity with analogous chemicals are important. In the non-radioactive local lymph-n...


    pub_type: 杂志文章


    authors: Yamano T,Shimizu M,Noda T

    更新日期:2003-08-28 00:00:00

  • Antioxidant activity of nasunin, an anthocyanin in eggplant peels.

    abstract::The free radical scavenging activities and inhibitory effect of lipid peroxidation of a delphinidin derivative in eggplant were investigated. Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside (nasunin), an anthocyanin, was isolated as purple colored crystals from eggplant peels. Using electron spin resonance spectrome...


    pub_type: 杂志文章


    authors: Noda Y,Kneyuki T,Igarashi K,Mori A,Packer L

    更新日期:2000-08-07 00:00:00

  • Preparation and properties of primary maintenance cultures of adult rabbit hepatocytes.

    abstract::Static and rotary cultures of adult rabbit hepatocytes can be produced reproducibly following their isolation by means of a simplified, inexpensive recycling perfusion system. Light and electron microscopic examination of the cultures showed that these hepatocytes retained the morphological characteristics of fully di...


    pub_type: 杂志文章


    authors: Poole A,Chasseaud LF,Bridges JW

    更新日期:1982-01-01 00:00:00

  • Suspended particulate matter in indoor air: adjuvants and allergen carriers.

    abstract::The overall purpose of this study was to investigate how airborne house dust particles may contribute to an allergic immune response, and thereby also to asthma and other respiratory symptoms. The following aims were set: first, to quantify and characterize indoor suspended particulate matter (SPM) with regard to amou...


    pub_type: 杂志文章


    authors: Ormstad H

    更新日期:2000-11-02 00:00:00

  • Inhibition of rat heart mitochondrial electron transport in vitro: implications for the cardiotoxic action of allylamine or its primary metabolite, acrolein.

    abstract::Allylamine (3-aminopropene) is a specific cardiac toxicant that causes aortic, valvular and myocardial lesions in many species. Myocardial necrosis can be observed 24 h after a single dose. Acute toxicity is believed to involve metabolism of allylamine to highly reactive acrolein (2-propenal). Allylamine has been show...


    pub_type: 杂志文章


    authors: Biagini RE,Toraason MA,Lynch DW,Winston GW

    更新日期:1990-05-14 00:00:00

  • Chemical sensitivity: symptom, syndrome or mechanism for disease?

    abstract::Several different meanings have been attached to the term "chemical sensitivity" by those who use it. Feeling ill from odors is a symptom reported by approximately one-third of the population. The syndrome of chemical sensitivity, frequently called "Multiple Chemical Sensitivity" or "MCS" has been the subject of three...


    pub_type: 杂志文章,评审


    authors: Miller CS

    更新日期:1996-07-17 00:00:00

  • Fusarenon-X induced apoptosis in HL-60 cells depends on caspase activation and cytochrome c release.

    abstract::Fusarenon-X (FX), a trichothecene mycotoxin, is well known to be cytotoxic to mammalian cells. Our previous study revealed that FX induced apoptosis in mouse thymocytes both in vivo and in vitro. We investigated the mode of apoptosis induced by FX using HL-60 cell culture. When FX at a final concentration of 0.5 micro...


    pub_type: 杂志文章


    authors: Miura K,Aminova L,Murayama Y

    更新日期:2002-03-20 00:00:00

  • Aspartame: review of recent experimental and observational data.

    abstract::In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studie...


    pub_type: 杂志文章,评审


    authors: Janssen PJ,van der Heijden CA

    更新日期:1988-06-01 00:00:00

  • The acute vascular effects of cadmium in the testis do not require the presence of Leydig cells.

    abstract::In order to test the hypothesis that Leydig cells are required for the acute toxic effect of cadmium on the testis, adult male rats were treated with the Leydig cell toxin ethane dimethanesulphonate (EDS). Four days later, when all Leydig cells are removed from the testis, the EDS treated and control rats were given a...


    pub_type: 杂志文章


    authors: Bergh AR

    更新日期:1990-08-01 00:00:00

  • Prenatal exposure to cypermethrin modulates rat NK cell cytotoxic functions.

    abstract::The synthetic pyrethroid insecticide, cypermethrin, was given during gestation to pregnant rats by gavage in corn oil. Peripheral blood and spleen cytotoxic activity of dams and their offspring were then evaluated at different times (30, 60, 90, 120 days) after birth. Pups showed a significant increase in peripheral b...


    pub_type: 杂志文章


    authors: Santoni G,Cantalamessa F,Mazzucca L,Romagnoli S,Piccoli M

    更新日期:1997-07-11 00:00:00

  • Effects of calcium and magnesium acetates on tissue distribution of carcinogenic doses of cadmium chloride in Wistar rats.

    abstract::Previous studies have shown that magnesium, unlike calcium, prevents cadmium carcinogenesis at the subcutaneous injection site, and that neither magnesium nor calcium has any significant influence on the production of testicular tumors by cadmium in rats. The present investigation attempts to disclose the nature of th...


    pub_type: 杂志文章


    authors: Kasprzak KS,Poirier LA

    更新日期:1985-03-15 00:00:00

  • Purification and characterization of diquat (1,1'-ethylene-2, 2'-dipyridylium)- metabolizing enzyme from paraquat-resistant rat liver cytosol.

    abstract::To establish a paraquat-resistant Wistar rat strain, we carried out continuous sister-brother mating among rats that survived high-dose intraperitoneal administration of paraquat dichloride (360 mg/kg). The percentages of paraquat-resistant rats among wild rats and among the fifth-generations were 7.1% and 20.6%, resp...


    pub_type: 杂志文章


    authors: Nakajima M,Nagao M,Iwasa M,Monma-Ohtaki J,Maeno Y,Koyama H,Seko-Nakamura Y,Isobe I,Takatori T

    更新日期:2000-11-23 00:00:00

  • Validation of a radial maze test for assessing learning and memory in rats.

    abstract::Choice behavior of rats in a radially symmetrical 6-arm maze, without food reward, was validated for assessing changes in learning and memory following treatment with 4 psychoactive agents. The test is designed for future use in routine toxicity studies with laboratory rodents. Each radial main arm of the maze leads t...


    pub_type: 杂志文章


    authors: Fitzgerald RE,Berres M,Schaeppi U

    更新日期:1988-05-01 00:00:00

  • Deltamethrin-induced oxidative damage and biochemical alterations in rat and its attenuation by Vitamin E.

    abstract::Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of deltamethrin to induce oxidative stress and changes in biochemical parameters and enzyme activities i...


    pub_type: 杂志文章


    authors: Yousef MI,Awad TI,Mohamed EH

    更新日期:2006-10-29 00:00:00

  • Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related.

    abstract::Use of the fluoroquinolone antibiotic trovafloxacin (TVX) was restricted due to idiosyncratic, drug-induced liver injury (IDILI). Previous studies demonstrated that tumor necrosis factor-alpha (TNF) and TVX interact to cause death of hepatocytes in vitro that was associated with prolonged activation of c-Jun N-termina...


    pub_type: 杂志文章


    authors: Beggs KM,Maiuri AR,Fullerton AM,Poulsen KL,Breier AB,Ganey PE,Roth RA

    更新日期:2015-05-04 00:00:00

  • Lipid peroxidation of rat myocardial tissue following daunomycin administration.

    abstract::Daunomycin-induced cardiotoxicity has been regarded to be the result of oxygen-mediated lipid peroxidation of cell membranes. The aim of the present work was to evaluate the extent of lipid peroxidation in rat heart after administration of this anticancer drug and, further, to examine possible activation of some endog...


    pub_type: 杂志文章


    authors: Papageorgiou G,Iliadis S,Botsoglou N,Dioudis C,Goulas A,Fletouris D,Dimitriadou-Vafiadou A

    更新日期:1998-03-13 00:00:00

  • In vitro and in vivo assessment of the irritation potential of different spin traps in human skin.

    abstract::No clinical data are available on the acute cutaneous toxicity of spin traps which are frequently used in combination with the electron paramagnetic resonance (EPR) technique for detection of free radicals and reactive oxygen/nitrogen species. The purpose of this study was to evaluate the acute dermatotoxicity of the ...


    pub_type: 杂志文章


    authors: Fuchs J,Groth N,Herrling T

    更新日期:2000-10-26 00:00:00

  • Immune-related gene polymorphisms in pulmonary diseases.

    abstract::Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nu...


    pub_type: 杂志文章,评审


    authors: Singh DP,Bagam P,Sahoo MK,Batra S

    更新日期:2017-05-15 00:00:00

  • Biochemical changes in subacute mycotoxicosis induced by T-2 toxin in rats.

    abstract::The intragastric administration to male Wistar rats of T-2 toxin at 1-1.3 mg/kg body weight for 7 days caused a sharp decrease in the liver activity of lysosomal enzymes: beta-galactosidase, beta-N-acetylglucosaminidase, alpha-mannosidase, cathepsins A, B, C and D and in the activity of enzymes of the 1st phase of met...


    pub_type: 杂志文章


    authors: Kravchenko LV,Tutelyan VA,Vasilyev AV,Kranauskas AE,Avrenyeva LI

    更新日期:1986-12-01 00:00:00

  • Historical perspective on risk assessment in the federal government.

    abstract::This article traces the evolution of risk assessment as an essential analytical tool in the federal government. In many programs and agencies, decisions cannot be made without the benefit of information from risk assessment. Although this analytical tool influences important public health and economic decisions, there...


    pub_type: 历史文章,杂志文章,评审


    authors: Graham JD

    更新日期:1995-09-01 00:00:00

  • The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines.

    abstract::A number of studies reported that the MTS in vitro cytotoxicity assay is a convenient method for assessing cell viability. The main features found with this assay are its ease of use, accuracy and rapid indication of toxicity. It might well be a useful tool in human health risk assessment if it can be shown that this ...


    pub_type: 杂志文章


    authors: Malich G,Markovic B,Winder C

    更新日期:1997-12-31 00:00:00

  • Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

    abstract::Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enz...


    pub_type: 杂志文章


    authors: Yousef MI,Awad TI,Elhag FA,Khaled FA

    更新日期:2007-06-25 00:00:00

  • Reproductive toxicity evaluation of vanadium in male mice.

    abstract::The reproductive toxicity of vanadium was studied in mice. Male Swiss mice were exposed to sodium metavanadate at doses of 0, 20, 40, 60, and 80 mg/kg per day given in the drinking water for 64 days. To evaluate the fertility of the vanadium-treated animals, males were mated with untreated females for 4 days. A signif...


    pub_type: 杂志文章


    authors: Llobet JM,Colomina MT,Sirvent JJ,Domingo JL,Corbella J

    更新日期:1993-06-11 00:00:00

  • Effect of viability of actinomycete spores on their ability to stimulate production of nitric oxide and reactive oxygen species in RAW264.7 macrophages.

    abstract::Spores of actinomycetes, mesophilic gram-positive bacteria, isolated from moldy houses, induced the expression of inducible NO-synthase (iNOS) with a subsequent NO-production in RAW264.7 macrophages. No differences were detected between production of nitric oxide (NO) by alive or irradiated spores of different strains...


    pub_type: 杂志文章


    authors: Hirvonen MR,Ruotsalainen M,Savolainen K,Nevalainen A

    更新日期:1997-12-26 00:00:00

  • The embryotoxic and osteolathyrogenic effects of semicarbazide.

    abstract::The osteolathyrogenic agent semicarbazide was assayed for its toxicity and teratogenicity using early embryos of the frog Xenopus laevis. The 96-h LC50 is 1504.20 mg/l while the 96-h EC50 is 76.28 mg/l. Embryo length is altered prior to the onset of other effects indicated by a reduction in stage of development. The m...


    pub_type: 杂志文章


    authors: Schultz TW,Dumont JN,Epler RG

    更新日期:1985-08-01 00:00:00

  • Oxidative stress and DNA damage in Fischer rats following acute exposure to trichloroethylene or perchloroethylene.

    abstract::Oxidative DNA damage is emerging as an biomarker of effect in studies assessing the health risks of occupational chemicals. Trichloroethylene (TCE) and perchloroethylene (PERC) are used in the dry cleaning industry and their metabolism can produce reactive oxygen compounds. The present study examined the potential for...


    pub_type: 杂志文章


    authors: Toraason M,Clark J,Dankovic D,Mathias P,Skaggs S,Walker C,Werren D

    更新日期:1999-10-29 00:00:00

  • Application of a discovery to targeted LC-MS proteomics approach to identify deregulated proteins associated with idiosyncratic liver toxicity in a rat model of LPS/diclofenac co-administration.

    abstract::Increasing experimental and clinical evidence suggest a contribution of non-drug related risk factors (e.g., underlying disease, bacterial/viral infection) to idiosyncratic drug reactions (IDR). Our previous work showed that co-treatment with bacterial endotoxin (LPS) and therapeutic doses of diclofenac (Dcl), an anal...


    pub_type: 杂志文章


    authors: Ramm S,Morissey B,Hernandez B,Rooney C,Pennington SR,Mally A

    更新日期:2015-05-04 00:00:00